Project description:The formation of the visual system is a complex multistep process that includes the establishment of proper connectivity of retinal ganglion cell (RGC) axon terminals with their relay neurons located in the brain. In mammals, the assembly of the different components of the visual circuit occurs at perinatal stages before eye opening. Upon reaching the target nuclei RGC axons extensively arborize and subsequently refine to establish the final connections. Spontaneous activity generated in the immature retina plays an essential role in the refinement of visual terminals at the main image-forming nuclei (IFN) that follow an eye-specific and retinotopic organization. However, the molecular mechanisms underlying spontaneous activity-dependent axon remodeling, and the influence of this activity in the connectivity of non-image forming nuclei (NIFN) that lack precise retinotopic maps and/or eye-specific segregation, are not well known. Here, by generating conditional mice with disturbed spontaneous retinal aneactivity and analyzing their retinal transcriptomic profiles, we identified novel players involved in axon refinement at the visual nuclei (e. g. Syt13). The analysis of visual projections in the NIFN of these mice revealed that correlated-retinal activity shapes final connectivity in non retinotopic or eye-specific segregating visual nuclei.
Project description:Since the discovery of the non-image-forming visual system, tremendous research efforts have been dedicated to understanding its mechanisms and functional roles. Original functions associated with the melanopsin system include the photoentrainment of circadian sleep-wake cycles and the pupillary light reflex. Recent findings, however, suggest a much broader involvement of this system in an array of physiologic responses to light. This newfound insight into the underlying function of the non-image-forming system has revealed the many connections to human pathology and attendant disease states, including seasonal affective disorder, migraine, glaucoma, inherited mitochondrial optic neuropathy, and sleep dysregulation of aging. In this review, the authors discuss in detail the clinical implications of the melanopsin system.
Project description:Neural circuits consist of highly precise connections among specific types of neurons that serve a common functional goal. How neurons distinguish among different synaptic targets to form functionally precise circuits remains largely unknown. Here, we show that during development, the adhesion molecule cadherin-6 (Cdh6) is expressed by a subset of retinal ganglion cells (RGCs) and also by their targets in the brain. All of the Cdh6-expressing retinorecipient nuclei mediate non-image-forming visual functions. A screen of mice expressing GFP in specific subsets of RGCs revealed that Cdh3-RGCs which also express Cdh6 selectively innervate Cdh6-expressing retinorecipient targets. Moreover, in Cdh6-deficient mice, the axons of Cdh3-RGCs fail to properly innervate their targets and instead project to other visual nuclei. These findings provide functional evidence that classical cadherins promote mammalian CNS circuit development by ensuring that axons of specific cell types connect to their appropriate synaptic targets.
Project description:Simulation theories of empathy hypothesize that empathizing with others' pain shares some common psychological computations with the processing of one's own pain. Support for this perspective has largely relied on functional neuroimaging evidence of an overlap between activations during the experience of physical pain and empathy for other people's pain. Here, we extend the functional overlap perspective to the neurochemical level and test whether a common physical painkiller, acetaminophen (paracetamol), can reduce empathy for another's pain. In two double-blind placebo-controlled experiments, participants rated perceived pain, personal distress and empathic concern in response to reading scenarios about another's physical or social pain, witnessing ostracism in the lab, or visualizing another study participant receiving painful noise blasts. As hypothesized, acetaminophen reduced empathy in response to others' pain. Acetaminophen also reduced the unpleasantness of noise blasts delivered to the participant, which mediated acetaminophen's effects on empathy. Together, these findings suggest that the physical painkiller acetaminophen reduces empathy for pain and provide a new perspective on the neurochemical bases of empathy. Because empathy regulates prosocial and antisocial behavior, these drug-induced reductions in empathy raise concerns about the broader social side effects of acetaminophen, which is taken by almost a quarter of adults in the United States each week.
Project description:UnlabelledPain can be influenced by its social context. We aimed to examine under controlled experimental conditions how empathy from a partner and personal attachment style affect pain report, tolerance, and facial expressions of pain. Fifty-four participants, divided into secure, anxious, and avoidant attachment style groups, underwent a cold pressor task with their partners present. We manipulated how much empathy the participants perceived that their partners had for them. We observed a significant main effect of perceived empathy on pain report, with greater pain reported in the high perceived empathy condition. No such effects were found for pain tolerance or facial display. We also found a significant interaction of empathy with attachment style group, with the avoidant group reporting and displaying less pain than the secure and the anxious groups in the high perceived empathy condition. No such findings were observed in the low empathy condition. These results suggest that empathy from one's partner may influence pain report beyond behavioral reactions. In addition, the amount of pain report and expression that people show in high empathy conditions depends on their attachment style.PerspectiveBelieving that one's partner feels high empathy for one's pain may lead individuals to rate the intensity of pain as higher. Individual differences in attachment style moderate this empathy effect.
Project description:Empathy relies on brain systems that support the interaction between an observer's mental state and cues about the others' experience. Beyond the core brain areas typically activated in pain empathy studies (insular and anterior cingulate cortices), the diversity of paradigms used may reveal secondary networks that subserve other more specific processes. A coordinate-based meta-analysis of fMRI experiments on pain empathy was conducted to obtain activation likelihood estimates along three factors and seven conditions: visual cues (body parts, facial expressions), visuospatial (first-person, thirdperson), and cognitive (self-, stimuli-, other-oriented tasks) perspectives. The core network was found across cues and perspectives, and common activation was observed in higher-order visual areas. Body-parts distinctly activated areas related with sensorimotor processing (superior and inferior parietal lobules, anterior insula) while facial expression distinctly involved the inferior frontal gyrus. Self- compared to other-perspective produced distinct activations in the left insula while stimulus- versus other-perspective produced distinctive responses in the inferior frontal and parietal lobules, precentral gyrus, and cerebellum. Pain empathy relies on a core network which is modulated by several secondary networks. The involvement of the latter seems to depend on the visual cues available and the observer's mental state that can be influenced by specific instructions.
Project description:The change in irradiance at dawn and dusk provides the primary cue for the entrainment of the mammalian circadian pacemaker. Irradiance detection has been ascribed largely to melanopsin-based phototransduction [1-5]. Here we examine the role of ultraviolet-sensitive (UVS) cones in the modulation of circadian behavior, sleep, and suprachiasmatic nucleus (SCN) electrical activity. UV light exposure leads to phase-shifting responses comparable to those of white light. Moreover, UV light exposure induces sleep in wild-type and melanopsin-deficient (Opn4(-/-)) mice with equal efficacy. Electrical recordings from the SCN of wild-type mice show that UV light elicits irradiance-dependent sustained responses that are similar to those induced by white light, with characteristic fast transient components occurring at the light transitions. These responses are retained in Opn4(-/-) mice and preserved under saturating photopic conditions. The sensitivity of phase-shifting responses to UV light is unaffected by the loss of rods but is severely attenuated by the additional loss of cones. Our data show that UVS cones play an important role in circadian and sleep regulation in mice.
Project description:Changing the visual body appearance by use of as virtual reality system, funny mirror, or binocular glasses has been reported to be helpful in rehabilitation of pain. However, there are interindividual differences in the analgesic effect of changing the visual body image. We hypothesized that a negative body image associated with changing the visual body appearance causes interindividual differences in the analgesic effect although the relationship between the visual body appearance and analgesic effect has not been clarified. We investigated whether a negative body image associated with changes in the visual body appearance increased pain. Twenty-five healthy individuals participated in this study. To evoke a negative body image, we applied the method of rubber hand illusion. We created an "injured rubber hand" to evoke unpleasantness associated with pain, a "hairy rubber hand" to evoke unpleasantness associated with embarrassment, and a "twisted rubber hand" to evoke unpleasantness associated with deviation from the concept of normality. We also created a "normal rubber hand" as a control. The pain threshold was measured while the participant observed the rubber hand using a device that measured pain caused by thermal stimuli. Body ownership experiences were elicited by observation of the injured rubber hand and hairy rubber hand as well as the normal rubber hand. Participants felt more unpleasantness by observing the injured rubber hand and hairy rubber hand than the normal rubber hand and twisted rubber hand (p<0.001). The pain threshold was lower under the injured rubber hand condition than with the other conditions (p<0.001). We conclude that a negative body appearance associated with pain can increase pain sensitivity.
Project description:Although it has been proposed that schizophrenia is characterized by impaired empathy, several recent studies found intact neural responses on tasks measuring the affective subdomain of empathy. This study further examined affective empathy in 21 schizophrenia outpatients and 21 healthy controls using a validated pain empathy paradigm with two components: (i) observing videos of people described as medical patients who were receiving a painful sound stimulation treatment; (ii) listening to the painful sounds (to create regions of interest). The observing videos component incorporated experimental manipulations of perspective taking (instructions to imagine 'Self' vs 'Other' experiencing pain) and cognitive appraisal (information about whether treatment was 'Effective' vs 'Not Effective'). When considering activation across experimental conditions, both groups showed similar dorsal anterior cingulate cortex (dACC) and anterior insula (AI) activation while merely observing others in pain. However, there were group differences associated with perspective taking: controls showed relatively greater dACC and AI activation for the Self vs Other contrast whereas patients showed relatively greater activation in these and additional regions for the Other vs Self contrast. Although patients demonstrated grossly intact neural activity while observing others in pain, they showed more subtle abnormalities when required to toggle between imagining themselves vs others experiencing pain.